Saha Renata, Goyal Abhinav, Yuen Jason, Oh Yoonbae, Bloom Robert P, Benally Onri J, Wu Kai, Netoff Theoden I, Low Walter C, Bennet Kevin E, Lee Kendall H, Shin Hojin, Wang Jian-Ping
Department of Electrical and Computer Engineering, University of Minnesota, Minneapolis, MN, United States.
Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, United States.
bioRxiv. 2023 May 25:2023.05.25.542334. doi: 10.1101/2023.05.25.542334.
Research into the role of neurotransmitters in regulating normal and pathologic brain functions has made significant progress. Yet, clinical trials that aim to improve therapeutic interventions do not take advantage of the changes in the neurochemistry that occur in real time during disease progression, drug interactions or response to pharmacological, cognitive, behavioral, and neuromodulation therapies. In this work, we used the WINCS tool to study the real time changes in dopamine release in rodent brains for the micromagnetic neuromodulation therapy.
Although still in its infancy, micromagnetic stimulation (µMS) using micro-meter sized coils or microcoils (μcoils) has shown incredible promise in spatially selective, galvanic contact free and highly focal neuromodulation. These μcoils are powered by a time-varying current which generates a magnetic field. As per Faraday's Laws of Electromagnetic Induction, this magnetic field induces an electric field in a conducting medium (here, the brain tissues). We used a solenoidal-shaped μcoil to stimulate the medial forebrain bundle (MFB) of the rodent brain . The evoked dopamine releases in the striatum were tracked in real time by carbon fiber microelectrodes (CFM) using fast scan cyclic voltammetry (FSCV).
Our experiments report that μcoils can successfully activate the MFB in rodent brains, triggering dopamine release . We further show that the successful release of dopamine upon micromagnetic stimulation is dependent on the orientation of the μcoil. Furthermore, varied intensities of µMS can control the concentration of dopamine releases in the striatum.
This work helps us better understand the brain and its conditions arising from a new therapeutic intervention, like µMS, at the level of neurotransmitter release. Despite its early stage, this study potentially paves the path for µMS to enter the clinical world as a precisely controlled and optimized neuromodulation therapy.
对神经递质在调节正常和病理性脑功能中作用的研究已取得显著进展。然而,旨在改善治疗干预措施的临床试验并未利用疾病进展、药物相互作用或对药理学、认知、行为和神经调节疗法的反应过程中实时发生的神经化学变化。在这项工作中,我们使用WINCS工具研究啮齿动物大脑中多巴胺释放的实时变化,用于微磁神经调节疗法。
尽管微磁刺激(µMS)仍处于起步阶段,但使用微米级线圈或微线圈(μ线圈)进行的微磁刺激在空间选择性、无电流接触和高度聚焦的神经调节方面已显示出巨大潜力。这些μ线圈由时变电流供电,该电流会产生磁场。根据法拉第电磁感应定律,该磁场在导电介质(此处为脑组织)中感应出电场。我们使用螺线管形状的μ线圈刺激啮齿动物大脑的内侧前脑束(MFB)。通过碳纤维微电极(CFM)使用快速扫描循环伏安法(FSCV)实时跟踪纹状体中诱发的多巴胺释放。
我们的实验表明,μ线圈可以成功激活啮齿动物大脑中的MFB,触发多巴胺释放。我们进一步表明,微磁刺激后多巴胺的成功释放取决于μ线圈的方向。此外,不同强度的µMS可以控制纹状体中多巴胺释放的浓度。
这项工作有助于我们在神经递质释放水平上更好地理解大脑及其因微磁刺激等新治疗干预措施而产生的状况。尽管尚处于早期阶段,但这项研究可能为微磁刺激作为一种精确控制和优化的神经调节疗法进入临床领域铺平道路。